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Compositions and methods for prognosis of ovarian cancer

a technology of ovarian cancer and prognosis, applied in the field of compositions and methods, can solve the problems of reduced expression of tumor suppressor genes, loss of mirna expression, oncogene activation, etc., and achieve the effect of short time to progression and short time to progression

Inactive Publication Date: 2011-05-05
ROSETTA GENOMICS +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016]In another aspect of the invention, the prognosis is time to progression of the disease in a subject, and the nucleic acids are selected from the group consisting of SEQ ID NOS: 4-7, 19-23, 55 and 71 and sequences at least about 80% identical thereto. According to some embodiments, an expression level of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 4-7, 19-21, 55 and 71 and sequences at least about 80% identical thereto above said threshold expression level is predictive of short time to progression. According to other embodiments, expression levels of a nucleic acid sequence selected from the group consisting of SEQ ID NO: 22-23 and sequences at least about 80% identical thereto below said threshold expression level is predictive of short time to progression.

Problems solved by technology

In some cases miRNA overexpression results in reduced expression of tumor suppressor genes, while loss of miRNA expression often leads to oncogene activation.

Method used

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  • Compositions and methods for prognosis of ovarian cancer
  • Compositions and methods for prognosis of ovarian cancer
  • Compositions and methods for prognosis of ovarian cancer

Examples

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example 1

Materials and Methods

[0176]a. Patients and samples

[0177]Patients, who were surgically treated for ovarian cancer at the Rabin Medical Center between January, 2000 and December, 2004 were identified. All pathology slides were re-evaluated by an expert pathologist. Tumor histology was established and the diagnosis of EOC was confirmed. Only serous papillary and endometrioid histology were included in the study. Patients found to have a synchronous endometrial malignancy were excluded. For each patient, a formalin-fixed paraffin embedded (FFPE) tumor sample was obtained and tumor cell content was evaluated by a pathologist. Only tumor samples with a minimum of 50% tumor tissue content were included. Patient charts were reviewed for clinicopathologic information—demographics, surgical procedure and findings, pathology, chemotherapy regimens and response, follow-up and survival. Optimal surgical cytoreduction was defined during the study period as the largest residual tumor diameter of 1...

example 2

miR Expression Patterns Correlate with Stage of Disease

[0188]Time to progression and survival were clearly linked to stage in the study cohort of patients. The microRNA expression were compared between stage I (n=19) and stage III (n=38) cases. 18 microRNAs (Table 2) were differentially expressed with p<0.05 (Mann-Whitney test), including for example hsa-miR-449b (SEQ ID NO: 22) (p=0.048). hsa-miR-200a (SEQ ID NO: 30) (p=0.00047) was also significant when allowing a False Discovery Rate (FDR) of 10%. Both of these microRNAs were more highly expressed in stage I ovarian cancers compared to stage III cases. Fold-change is the ratio of the median signals in the two groups.

TABLE 2miRSEQ ID NO:p-valuefold-changehigher inhsa-miR-200a300.000472.10Stage Ihsa-miR-200b400.00431.63Stage Ihsa-miR-34a360.00661.69Stage Ihsa-miR-513a-5p410.00685.32Stage Ihsa-miR-509-3p420.007410.3Stage Ihsa-miR-509-3-5p430.0174.01Stage Ihsa-miR-574-5p440.0451.24Stage Ihsa-miR-449b220.0484.61Stage Ihsa-miR-423-3p45...

example 3

miR Expression Patterns in Patients with Stage III Disease Correlate with Response to Platinum Therapy

[0191]The relation between miR expression and disease progression was studied. Since patient prognosis and disease characteristics vary for different stages of the disease, the inventors focused on the larger, higher risk group of patients in stage III. 25 patients achieved a complete response with no recurrence within 6 months of the end of treatment, and were termed platinum-sensitive. Twelve patients had rapid progression of the disease (partial response or recurrence within 6 months of the end of treatment) and were termed platinum-resistant. The patient censored before 6 months was not included in this analysis.

[0192]miR expression patterns were examined in tumors from platinum-resistant stage III patients (n=12) and in tumors from platinum-sensitive stage III patients (n=25). As shown in table 3, hsa-miR-199a-3p (SEQ ID NO: 1), hsa-miR-27a (SEQ ID NO: 4), hsa-miR-23a (SEQ ID N...

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Abstract

Described herein are compositions and methods for the prediction of the prognosis of ovarian cancer subjects. The present invention further provides methods for distinguishing between histological subtypes of ovarian cancer tumors, and also methods and compositions for the treatment or prevention of ovarian cancer. Specifically the invention relates to microRNA molecules associated with said methods and compositions, as well as various nucleic acid molecules relating thereto or derived therefrom.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]The present application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61 / 073,036, filed Jun. 17, 2008 and U.S. Provisional Application No. 61 / 108,556, filed Oct. 27, 2008 which are herein incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]The invention relates to compositions and methods for the prediction of survival, time to progression, and response to therapy in ovarian cancer subjects. Specifically the invention relates to microRNA molecules associated with the prognosis of ovarian cancer subjects, as well as various nucleic acid molecules relating thereto or derived therefrom.BACKGROUND OF THE INVENTION[0003]Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related deaths in women in the United States and the leading cause of gynecologic cancer related deaths (Jemal A, Siegel et. al, Cancer statistics, 2007, CA Cancer J Clin 2007; 57:43-66). Annually, there are mo...

Claims

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Application Information

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IPC IPC(8): A61K31/7088C12Q1/68C40B30/04A61P35/00
CPCC12Q1/6886C12Q2600/178C12Q2600/118C12Q2600/112A61K31/713A61P35/00A61K45/00C12Q2600/106C12Q2600/16
Inventor HOSEN, MOSHELITHWICK YANAI, GILAEITAN, RAM
Owner ROSETTA GENOMICS